A catalog of articles written by award winning investigative journalist, Evelyn Pringle.

Thursday, August 5, 2010

Roche Puts Accutane Profits Over Lives of Consumers

Evelyn Pringle August 31, 2006

In 1985, Accutane's package insert directed at doctors first mentioned reports of depression in patients taking the acne drug, which means that more than 20 years ago, Hoffman-LaRoche at least suspected there might be a risk of depression and suicide by persons taking the drug.

However, Roche's financial records show that the company is not about to let a little thing like the death of its customers get in the way of corporate profits, because the drug is still a best seller and young people with no history of depression who take it are still killing themselves.

On November 14, 2004, BBC News reported that Jon Medland, 22, in the final year of medical school at Manchester University, hanged himself at his student lodgings on January 13, 2004 while on Accutane.

When questioned about the incident, Roche told BBC News that the drug carried a warning of possible mood changes and depression, but said "no causal link had been established between the drug and either depression or suicide."

Less than a year later, in September 2005, BBC News reported that David Roberts, 21, had been on the drug for two months when he hanged himself near his Liverpool home.

And once again, according to BBC News, "Roche insists there is no proven relationship between the drug and depression."

However, David's father, Fred Roberts, said he could think of no other explanation for the tragedy. "David was the most happy-go-lucky, carefree lad you could ever hope to meet. He had plenty of friends, he enjoyed going out, he had a happy family life."

"His acne wasn't severe at all. He had a few spots and, like any young person, he wanted to get rid of them."

"The change in him was so sudden," Mr Roberts said, "there's no other reason for it than the effect of this drug."

On January 15, 2006, 15-year-old Justin Zimmer, of Menasha, Wisconsin, shot himself and his parents blame Accutane.

Justin's parents and a friend told the Appleton Post Crescent on July 18, 2006, that he gave no indication that he was depressed and that he was all excited about getting his driver's license in a couple of weeks.

Roche's comments to the BBC are clearly dishonest considering that in 1986, doctors were notified that Accutane users who became depressed saw their depression lift when they stopped taking the drug but return when they were placed back on the medication. Doctors were also informed that simply stopping Accutane therapy might not be sufficient to treat the depression and that follow up on the depression might be necessary.

The agency issued a MedWatch alert in February 1998, that said due to the adverse event reports received, the FDA felt there was sufficient cause to strengthen the warning on the Accutane label to include the risk of psychosis and suicidal thoughts and actions.

The February 23, 1998, FDA Memorandum, "Isotretinoin and Depression: Spontaneous Report Data," listed 31 cases of suicide, suicide attempt or suicide ideation associated with Accutane. Of those cases, 12 were suicides, 9 were male, 2 were female, and 1 unknown, and the average age was 17. The event occurred on average, 88 days after the patient started taking the drug.

The FDA acknowledged in the memorandum that for "the majority, there was no antecedent history of depression and the patients were not noted or known to be depressed in the time period prior to their suicide."

During a US House Oversight and Investigation Subcommittee hearing on the Safety Issues Relating to Accutane, on December 11, 2002, internal documents from the nation's regulatory agencies were entered into the record that revealed that public health officials had been voicing concerns about patients committing suicide while on Accutane for well over a decade.

For instance, a 1998 memo from the FDA's medical officer in charge of Accutane states: "Given all the pieces of evidence available, it is difficult to avoid the conclusion that Accutane can adversely affect the adult human brain in clinically significant ways and that Accutane use is associated with severe psychiatric disease in some patients."

The memo recommends "active consideration of removal of Accutane from the market."

But instead of removing the drug from the market, on February 25, 1998, the FDA required Roche to add the following bold-face warning to drug's physician package insert:

"WARNINGS - Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events."

"ADVERSE REACTIONS - In the postmarketing period, a number of patients treated with Accutane have reported depression, psychosis and rarely, suicidal, ideation, suicide attempts and suicide. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy."

In perverse twist of logic, in the same year, Roche began actively marketing Accutane as a treatment for depression, under the theory that it could help people who were suffering from depression due to poor self-image as a result of acne.

On March 5, 1998, Roche received a letter from the FDA stating that such promotion was false and misleading, and that Accutane had never been approved for the treatment of depression, and that in fact, just the opposite was true. The letter stated in relevant part:

"Roche ... has not systematically studied the ability of Accutane to modify or prevent such illnesses as depression and has presented no basis for asserting that Accutane is effective in improving the psychosocial and emotional well-being of such patients.

"This claim is particularly troublesome in light of information recently presented in a Dear Doctor letter, that Accutane may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."

The FDA also instructed Roche to "prominently disclose information about the psychiatric disorders described in the warnings section of the revised labeling" in Accutane advertisements.

In September 1998, the FDA presented an Advisory Panel with 37 cases of suicide attributed to Accutane since 1983. However, the number was later changed to 44 suicides after Roche corrected its calculations.

The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events, designed to support the FDA's post-marketing surveillance program of all approved drugs.

The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.

The results of a review of AERS by congressional staffers working on behalf of Congressman, Bart Stupak (D-MI), revealed during an October 5, 2000, hearing, reported 54 more suicides by persons on Accutane after the FDA issued its MedWatch in 1998.

In 2004, the Alliance for Human Research Protection, asked Keith Altman, an Adverse Drug Reaction Statistics Analyst, to analyze the FDA's Medwatch database for drug-linked suicides by children under the age of 18. The analysis found that between 1989 and June 2003, there were 216 reports of drug-linked suicides, and 72 were associated with Accutane.

The Alliance points out that MedWatch reflects approximately 1% of actual adverse events, so 72 Accutane suicide reports could represent as many as 7,200 suicides.

Congressman Bart Stupak, lost his son, BJ, to suicide on Mother's Day, May 14, 2000, at the age of 17, from a self-inflicted gunshot wound and BJ was on Accutane at the time of his death.

On December 11, 2002, Rep Stupak told the audience at the Safety Issues Surrounding Accutane Hearing that, "Anyone who knew BJ could not understand why a young man with such an outgoing personality and bright future would end his own life."

After his suicide, BJ's mother, Laurie, checked out Accutane on the Internet and found many adverse events associated with the drug that they was never told about.

But the most disturbing find she said, was the February 1998 MedWatch stating, "The FDA is advising consumers and health care providers of new safety information regarding the prescription anti-acne drug Accutane (isotretinoin) and isolated reports of depression, psychosis, and rarely suicidal thoughts and actions."

"After we found the MedWatch," Rep Stupak said, "I wondered why the FDA put out this warning, 18 years after the drug was approved?"

"More important," he continued, "why weren't these warnings on BJ's Accutane package which had been revised 4 months after the MedWatch was issued?"

Two other couples testified at the hearing about their sons who had no history of depression, but yet committed suicide while taking Accutane. The spontaneity of the suicides became the center piece of discussion between committee members and witnesses during the hearing.

Susan and Martin Turney from Watertown, New York testified about their 16-year-old son, Matthew, who took his own life on March 14, 2001, and was on Accutane at the time of his death.

In retracing the days leading up to Matt's death, nothing indicated that anything was wrong. The night before the suicide, everything was normal his parents recalled. The family had a nice dinner together, talked about the day's events and joked and laughed with each other like always.

The next morning, Matt got up for school as usual. Before leaving to catch the bus, he looked at his father, smiled and said "Good Bye," and yelled, "Good Bye Mom. I love you," to his mother who was in another room, just like he did every morning.

By all accounts, Matt was fine at school that day. He talked to his guidance counselor about a program she had recommended for the next year. He asked a girl to a dance and she agreed to go. He took a couple of tests and did well.

On the bus ride home, Matt sat with his friends and laughed and fooled around just like any other day. He got off the bus and stopped to pick up the newspaper and mail as usual. He took off his shoes in the entryway, placed the mail and newspaper on the kitchen counter as he always did, and went into his room and hung up his coat.

His parents say it is at this point that Matt's normal routine changed. He did not turn on the TV, or get a snack or check his email as usual. Instead, he apparently went into the master bedroom, unlocked the gun case, took out a gun and shot himself.

His father came home from work and yelled "Hello" to Matt, but got no response so he went looking for him and found Matt on the floor of the bedroom with no heartbeat.

While answering questions from police at the hospital, Matt's parents were asked if Matt was taking any medication and they said Accutane. As soon as they answered, they remembered a TV Dateline program about the parents whose son committed suicide while on Accutane.

After watching the program Matt and his mother had went to the Dermatologist to discuss the story and their concerns about Accutane. The Dermatologist said that there had been a couple of unsubstantiated cases of depression and suicide, but that there was no scientific proof that Accutane could cause it and that Matt "didn't fit the profile anyway."

Matt's parents told the committee how they later found out that Accutane was supposed to be reserved for the most severe cases of nodular, cystic acne and provided the panel with a school picture of their son taken about 2 weeks before he started on Accutane that showed he did not have a severe acne problem.

"After talking to all of Matt's friends, family, teachers, and co-workers," his father told the committee, "we confirmed what we had already known, Matthew was not depressed!"

"His sudden death came as a shock to every person who knew Matt, including us, his parents," he said. Matt's suicide was "spontaneous," his parents said:

"There was no depression. There was no warning. There was nothing for us to look for. There was no reason for his death, other than Accutane."

Michael and Caroline Bencz also testified at the hearing about how their son, James, committed suicide without any sign that he was depressed or troubled. They told the panel that at the time of his death, he had everything to live for stating:

"James was not the person anyone would expect to commit suicide. He had friends and family. He had financial and personal success. He had plans for the future - both near and long term.

"The week James died, he was to leave on a skiing trip to Austria with a few of his firefighter buddies. James had plans for his future, and death was not in that plan."

"He was witty, humorous, talented, a great sportsman, intelligent, and highly competitive," his parent said, "but most of all, above all that, a wonderful human being.

In late 2001, they told the panel, they learned that a doctor prescribed Accutane for James. These parents also provided the committee with a picture of their to show that he never had a severe acne problem. All they could figure out was that maybe the skin diving suit he wore may have irritated his skin on his neck and back.

The last day they heard from James, on February 23, 2002, he called to say he did not feel well, that he had a headache. His last words to his parents were: "I don't feel too good, I'm going to try to get some sleep."

Over the next few days they did not hear from James which was very unusual. It was not like him, his parents said, to disappear for days at a time without letting anyone know where he was.

When he did not turn up, a massive man hunt was conducted, and he was eventually found on March 4, 2002, at the bottom of a lake, with a 44 pound barbell strapped to his body. A lake where James and his sister used to sit as children skipping rocks.

He died, his father told the committee, "under circumstances so bizarre for someone like James - a diver, a firefighter, and an athlete - with so much to live for, and so many future plans."

"We wish every minute of every day that we had never heard of that drug," they told the committee. "It took our son, our life as we know it, and left us with huge craters in our hearts that can never be filled in again."

These reports of inexplicable suicides were alarming to members of the committee. "Is it possible that this medication has an effect, an action that results in spontaneous, impulsive, self destructive behavior that is different from that which occurs from a clinical depression?," Congressman Ted Strickland (D-OH), who has a PhD in psychology, asked.

"I know of no clinical concept of depression that has an instantaneous onset and what we've heard described are people who are emotionally," Rep Strickland said, "psychologically healthy with none of the clinical signs of depression spontaneously doing something to themselves."

"So I'm wondering," he concluded, "if we are dealing here with something other than depression, and that we ought to recognize that."

The FDA Office of Drug Safety keeps a monthly cumulative count of psychiatric adverse event reports in AERS. According to Dr Janet Woodcock, Director of the Center for Drug Evaluation and Research, at the hearing, as of November 30, 2002, AERS contained 3,104 reports with at least one reported psychiatric event.

The FDA is aware of 173 reports of suicide in association with Accutane, she told the panel. She noted that the FDA had requested quarterly summaries of psychiatric events from Roche and said the most recent summary through August 2002 indicated approximately 6,000 additional reports that include psychiatric events

Because the 173 cases of suicides ware based on self reporting, experts say that figure is highly suspect and that being as few as 1% of suicides are reported as adverse events, it could mean that the actual number of suicides may be as high as 17,000.

During his December 11, 2002 statement to the committee, Congressman Stupak pointed the finger of blame directly at the FDA when stating:

"Accutane is a powerful, dangerous drug with devastating consequences for some patients. The birth defects caused by Accutane are horrific. The FDA's response to the birth defects and psychiatric events has been inadequate, irresponsible and unacceptable. Thousands of babies, teenagers, and young adults have died prematurely.

"While the FDA has been aware of the birth defects since at least 1982 and the psychiatric injuries since 1985, their responsibility to protect the public has been inconsistent and without direction."

There is no debate about whether Accutane is a moneymaker. According to the Associated Press on August 21, 2006, patients usually take it for up to a year at a cost of $10 to $15 per day. And in the December 11, 2002 hearing, Congressman Stupak turned the attention of the committee to Roche's conduct of putting profits before people and stated:

"They have done everything possible to prevent the American people from learning of the psychiatric injuries and deaths associated with Accutane. Even, today ... Roche will deny any casual effect of Accutane with the abortions, deaths, and suicides caused by their product."

"We cannot allow the drug manufacturer and the FDA to continue to turn a blind eye to the lives lost, families devastated and dreams dashed by an acne drug," he said.

"The American people, our children," he said, "are not collateral damage in the scheme of corporate profits!"